Ultragenyx Phase Three Failure Triggers Program Review

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) said on Sept. 2 that its Phase 3 Aspire trial of apazunersen (GTX-102) in Angelman syndrome failed to meet the primary and a key secondary endpoint. The company announced a program review and plans for significant expense reductions to support its commercial business.

Aspire Trial Missed Endpoints

Ultragenyx said in a press release that the Aspire trial did not achieve its primary endpoint, the change from baseline in the Bayley-4 cognitive raw score, nor the key secondary endpoint, the net response in the Multidomain Responder Index (MDRI). The company reported no differences between treated and control groups on these measures to support efficacy. The safety profile was consistent with earlier Phase 1/2 studies.

The release noted apazunersen had received Breakthrough Therapy, Orphan Drug, Rare Pediatric Disease, and Fast Track designations from the FDA, as well as Orphan and PRIME designations from the European Medicines Agency. It did not report any new regulatory actions tied to the trial results.

Program Review and Market Reaction

Ultragenyx said it will evaluate the apazunersen program and decide on its future. It also plans to assess operations and implement significant expense reductions while supporting its growing commercial business. The company did not provide quantitative financial guidance.

Shares fell sharply after the announcement, dropping in after-hours trading on Sept. 2 and plunging more than 40% in premarket trading on Sept. 3. The late-stage failure and the company’s decision to reassess the program shifted management’s near-term focus toward preserving resources for its commercial operations as it determines the drug’s disposition.